The capacity for mammalian limb regeneration remains almost entirely unexplored, largely because usable experimental models have not been available. Investigations on the regeneration of amputated limbs in neonatal opossums indicate that marsupials may serve as a useful and convenient experimental system. The immature state of newborn marsupial young and their accessibility in the maternal pouch provide conditions for both successful regeneration and ease of experimental manipulation. The finding that young children can fully regenerate whole amputated fingertips points to the need for such an experimental model. These observations indicate that humans are capable of an extensive regenerative response, and suggest that there is no inherent cytological basis for the failure of adult mammals to regenerate amputated extremities. The objective of this proposal is to establish a convenient, reliable and safe marsupial model for studying mammalian limb regeneration. The mouse opossum, Marmosa, will be the primary focus of this study. The regenerative ability of amputated limbs of Marmosa neonates will be assessed by morphological and biochemical studies. The course of regeneration will be followed by light and electron microscopy and the critical time period during which regeneration can occur will be identified. Protein synthesis during regeneration will be analyzed by slab gel electrophoresis and autoradiography. These studies should lead to insights into the nature of mammalian limb regeneration and the effects of maturation on tissue repair and regenerative ability. They may also provide information on the clinical management of amputation injuries and on approaches to maximizing the generative potential following amputation.